Tumor-on-a-chip models combined with mini-tissues or organoids for engineering tumor tissues.

The integration of tumor-on-a-chip technology with mini-tissues or organoids has emerged as a powerful approach in cancer research and drug development. This review provides an extensive examination of the diverse biofabrication methods employed to create mini-tissues, including 3D bioprinting, spheroids, microfluidic systems, and self-assembly techniques using cell-laden hydrogels. Furthermore, it explores various approaches for fabricating organ-on-a-chip platforms. This paper highlights the synergistic potential of combining these technologies to create tumor-on-a-chip models that mimic the complex tumor microenvironment and offer unique insights into cancer biology and therapeutic responses.

Macroscale pseudo-spheroids fabricated using methacrylated collagen-coated cells.

Rationale: Cell spheroids have shown great promise as tools for creating effective three-dimensional (3D) tissue models, facilitating tissue reconstruction and organoid development, due to their high cell density and efficient cellular interactions. However, a significant challenge persists in creating large-scale tissue structures with a 3D geometrical architecture using spheroids, due to the continual condensation and reorganization of cells and their environments. Methods: The spherical cell aggregates (pseudo-cell spheroids) or macroscale cell aggregates were obtained by coating each adipose-derived stem cell (hASC) with methacrylated collagen (Col-Ma). Subsequently, the coated cells were printed into an alginate supporting bath and photocrosslinked through exposure to UV light. To assess the effectiveness of this procedure on regenerative potential, the generated cell aggregates were compared with conventional cell spheroids and bioprinted cell constructs using immunofluorescent staining and quantification of myogenic-related gene expressions. Moreover, the bioconstructs were implanted into a mouse model with volumetric muscle loss to further elucidate their regenerative and functional recovery properties. Results: The use of Col-Ma as a cell-coating material enables the rapid and physical aggregation of cells within several hours, regardless of the cell type. Furthermore, Col-Ma-coated cell aggregates can provide relatively lower hypoxic conditions than cell spheroids fabricated using the hanging drop method owing to the thin porous Col-Ma layer coated on the cells. In addition, the resulting structures maintain their geometrical architecture following cell fusion and possess the potential for efficient scale-up and 3D complex shape formation, making them more suitable for clinical applications than conventional cell spheroids. Finally, the feasibility of the Col-Ma-coated cylindrical human adipose-derived stem cells aggregates was assessed through implantation in a mouse volumetric muscle loss model, showing a significantly higher regenerative ability of muscle tissue than the normally bioprinted cell construct. Conclusion: Our newly proposed method has meaningful potential for various tissue engineering applications, supported by the improved cellular activities and efficient muscle regeneration observed in both in vitro and in vivo studies, and organ-chip models.

Biopolymers and Their Application in Bioprinting Processes for Dental Tissue Engineering.

Dental tissues are composed of multiple tissues with complex organization, such as dentin, gingiva, periodontal ligament, and alveolar bone. These tissues have different mechanical and biological properties that are essential for their functions. Therefore, dental diseases and injuries pose significant challenges for restorative dentistry, as they require innovative strategies to regenerate damaged or missing dental tissues. Biomimetic bioconstructs that can effectively integrate with native tissues and restore their functionalities are desirable for dental tissue regeneration. However, fabricating such bioconstructs is challenging due to the diversity and complexity of dental tissues. This review provides a comprehensive overview of the recent developments in polymer-based tissue engineering and three-dimensional (3D) printing technologies for dental tissue regeneration. It also discusses the current state-of-the-art, focusing on key techniques, such as polymeric biomaterials and 3D printing with or without cells, used in tissue engineering for dental tissues. Moreover, the final section of this paper identifies the challenges and future directions of this promising research field.

Fabrication of self-assembled core-sheath microfibers via formulation of alginate-based bioinks.

Core-sheath microfibrous structures are widely used in various tissue engineering applications and drug delivery systems. However, the fabrication of the various core-sheath structures using a 3D printing process supplemented with a coaxial nozzle has been challenging due to the center positioning of the core nozzle enclosed in the bigger shell nozzle. In this work, we developed a new 3D printing process using an alginate-based bioink (a mixture of photo-crosslinkable hydrogel and alginate) and its in situ crosslinking process within a single glass nozzle of the 3D printer. By manipulating the alginate weight fraction, UV intensity, flow rate, and nozzle moving speed, we could fabricate various self-assembled core-sheath structures (straight, wavy, and crimped microfibers in the core region of the structure) in which the photocrosslinked hydrogel resided in the core, and alginate was positioned in the sheath region, like a virtual coaxial nozzle.

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications.

A spheroid is a complex, spherical cellular aggregate supporting cell-cell and cell-matrix interactions in an environment that mimics the real-world situation. In terms of tissue engineering, spheroids are important building blocks that replace two-dimensional cell cultures. Spheroids replicate tissue physiological activities. The use of spheroids with/without scaffolds yields structures that engage in desired activities and replicate the complicated geometry of three-dimensional tissues. In this mini-review, we describe conventional and novel methods by which scaffold-free and scaffolded spheroids may be fabricated and discuss their applications in tissue regeneration and future perspectives.

An in vitro model using spheroids-laden nanofibrous structures for attaining high degree of myoblast alignment and differentiation.

A spheroid is an aggregation of single cells with structural and functional characteristics similar to those of 3D native tissues, and it has been utilized as one of the typical in vitro three-dimensional (3D) cell models. Scaffold-free spheroids provide outstanding reflection of tissue complexity in a 3D in vivo-like environment, but they can neither fabricate realistic macroscale 3D complex structures without avoiding necrosis nor receive direct external stimuli (i.e., stimuli from mechanical or topographical cues). Here, we propose a spheroid-laden electrospinning process to obtain in vitro model achieved using the synergistic effect of the unique bioactive components provided by the spheroids and stimulating effects provided by the aligned nanofibers. Methods: To show the functional activity of the spheroid-laden structures, we used myoblast-spheroids to obtain skeletal muscle, comprising highly aligned myotubes, utilizing an uniaxially arranged topographical cue. The spheroid-electrospinning was used to align spheroids directly by embedding them in aligned alginate nanofibers, which were controlled with various materials and processing parameters. Results: The spheroids laden in the alginate nanofibers showed high cell viability (>90%) and was compared with that of a cell-laden alginate nanofiber that was electrospun with single cells. Consequently, the spheroids laden in the aligned nanofibers showed a significantly higher degree of myotube formation and maturation. Conclusion: Results suggested that the in vitro model using electrospun spheroids could potentially be employed to understand myogenic responses for various in vitro drug tests.

Angiogenic factors secreted from human ASC spheroids entrapped in an alginate-based hierarchical structure via combined 3D printing/electrospinning system.

Human adipose-derived stem cell spheroids have been widely used in the treatment or regeneration of damaged skin tissues, and their success is believed to be due in part to angiogenic factors released from the spheroids. To achieve the sustained release of bioactive components from implanted spheroids within a defective area, the use of a biocompatible scaffolding biomaterial is required. In this study, we developed an alginate-based scaffolding structure, which was processed using three-dimensional printing and electrospinning for use as a spheroid-entrapping structure. A micro-sized alginate strut and electrospun alginate nanofibers functioned not only to firmly entrap the spheroids, but also to enable the stable release of various angiogenic and wound healing-related factors. We also demonstrated the function of these factors using a tube-forming assay and found that conditioned media from the spheroid-scaffold group improved capillary-like structure formation in human umbilical vein endothelial cells compared to the single cell-scaffold group. Our results suggest that this spheroid-entrapping alginate hybrid structure could represent a new platform for stem cell therapy using spheroid transplantation.

Rasch Analysis of the Korean Parenting Stress Index Short Form (K-PSI-SF) in Mothers of Children with Cerebral Palsy.

The purpose of this study was to investigate the psychometric characteristics of the Korean Parenting Stress Index Short Form (K-PSI-SF) for mothers of children with cerebral palsy (CP) by using a Rasch analysis. The participants were 114 mothers of children with CP whose ages ranged from 2.79 to 11.90 years. The K-PSI-SF consists of 36 items, with a 5-point Likert scale grading along three subscales (Parent Distress, Parent-Child Dysfunctional Interaction, and Difficult Child). The response data were analyzed, and we determined the item fitness and item difficulty, rating scale fit, and separation index. The results show that two items did not have the required fitness. After these two items were deleted, the means of the 34 items in two of the subscales were statistically different from those of the original 36 items. Our analysis of the item difficulty identified the need to add easier question items. The 5-point Likert scale used in the questionnaire was found to be appropriate. This significance of this study is that it suggested the need to modify item fitness and difficulty level, as it identified the psychometric characteristics of the K-PSI-SF through a Rasch analysis based on the item response theory.

Skeletal myotube formation enhanced through fibrillated collagen nanofibers coated on a 3D-printed polycaprolactone surface.

This work focused on considering the cellular responses of the growth and differentiation of myoblasts, C2C12, on fibrillated collagen-coated poly(ε-caprolactone) (PCL) surfaces. Through a fibrillation processing window using NaCl and collagen weight fractions, collagen fibril coating density can be controlled. Three different collagen-fibril densities coated on PCL strut were used to investigate the effects of the collagen fibril on the myoblast activities. After physical and cellular analyses of the scaffolds, such as surface morphology, fibronectin absorption, wettability, and mechanical properties, the rate of cell growth and the proficiency of the myoblasts to develop skeletal myotubes were evaluated. Based on the results, although the coated collagen nanofibers were randomly distributed, the fibrillated collagen layer with the appropriate density on the PCL surface promoted a greater myotube formation than that of the control, which had no fibrillated collagen. In particular, relatively higher densities of collagen fibril showed significantly greater myotube formation than those of the control (not-fibrillated collagen-coated on the PCL surface) and lower density of collagen fibril.

The psychometric properties of the Childhood Health Assessment Questionnaire (CHAQ) in children with cerebral palsy.

BACKGROUND: The evaluation of children with cerebral palsy (CP) focuses on activity level measurement to examine the effect of health-care interventions on their physical functioning in the home, school, and community settings. This study aimed to identify the psychometric properties of the Korean version of the Childhood Health Assessment Questionnaire (CHAQ) by applying the Rasch model. The use of the Rasch model has an advantage in that item characteristic curve estimation is not affected by the characteristics of subject groups. METHODS: Data were collected from 65 children with CP aged 75-190 months using the Korean version of the CHAQ. Response data were analyzed according to the Rasch model, and item fitness and difficulty and the appropriateness and reliability of the rating scale were evaluated. RESULTS: Among the 30 items of the Korean version of the CHAQ, two items (nail-cutting and opening a bottle cap that was already opened) were shown to be misfit items with low fitness. The analysis results for item difficulty indicated the requirement for modification of item difficulty, pointing out the need for the addition of question items with both higher and lower difficulty. The use of 4-point rating scale in the evaluation questionnaire was shown to be appropriate. With respect to analysis outcomes, the subjects' separation reliability value and separation index were 0.97 and 5.92, respectively. In contrast, the separation reliability value and separation index for the question items were 0.95 and 4.51, respectively. CONCLUSIONS: The results of this study suggest the need for the modification of item fitness and difficulty. The psychometric properties of the Korean version of the CHAQ were identified using the item response theory-based Rasch analysis.